Effects of Acute Administration of Adipokinetic Hormone on Depression, Anxiety, Pain, Locomotion and Memory in Mice

Abstract

The neurosecretory cells in the corpus cardiacum of insects synthesize a set of hormones that are called adipokinetic, hypertrehalosemic or hyperprolinemic depending on the insect in question. They are the Adipokinetic Hormone/Red Pigment-Concentrating Hormone (AKH/RPCH) family of peptides. The present study investigated the effects of acute administration of Locusta Migratoria (Locmi-AKHII) and Anax Imperator (Anaim-AKH) on depression, anxiety, pain (analgesy), locomotion and memory in mice in forced swimming (FST), elevated plus maze (EPM), hot plate, locomotor activity and passive avoidance tests. Both Locmi-AKH-II (4 mg/kg) and Anaim-AKH (0.25 and 0.50 mg/kg) decreased immobility time (in sec, s) in the FST test. Anaim-AKH (0.5 and 1 mg/kg) increased the percentage of time spent in open arms/total time spent and the percentage of the number of open arm/total arm entries in the EPM test. Anaim-AKH (1 and 2 mg/kg) significantly increased latency (s) (initial time passed) for mice to lick their hind paws or jumping in the hot plate test. Anaim-AKH (4 mg/kg) significantly decreased the total distance (cm) moved, or the speed (cm/s) of movement of the animals in the locomotor activity test. Neither Locmi-AKH-II nor Anaim-AKH altered the retention latency (s) in the passive avoidance test. Both Locmi-AKH-II and Anaim-AKH exerted antidepressant effects, while only Anaim-AKH had anxiolytic and analgesic effects when administered acutely. Anaim-AKH diminished locomotion at higher doses while Locmi-AKH-II had no such effects. Neither Locmi-AKH-II nor Anaim-AKH disturbed learning and memory when acutely administered. Data of our studies suggest clinical potentials of AKH to be used in depression, anxiety and pain without disturbing memory.

Effects of the adipokinetic hormone/red pigment‐concentrating hormone (AKH/RPCH) family of peptides on MK‐801‐induced schizophrenia models

“…In the AAPA test, we administered the drugs subchronically and observed no memory deficit in naive animals. Similarly, AKH caused no memory deterioration in the passive avoidance test after acute administration in our recent study . This supports that the AKH/RPCH family of peptides do not cause psychosis or memory deterioration in naive animals.…”

“…For example, in the AAPA test, Ani‐AKH reversed hyperlocomotion caused by MK‐801 while Lia‐AKH had a partial effect, while Pht‐HrTH increased the total distance moved when combined with MK‐801. In our recent studies, we found that when these hormones were administered chronically, they all increased locomotion , while Ani‐AKH diminished locomotion at the 4‐mg/kg dose when administered acutely . In the AAPA test, we administered the drugs subchronically and Ani‐AKH decreased MK‐801‐induced hyperlocomotion, a finding that corresponded with our previous study findings .…”

“…The intranasal administration of oxytocin has been proposed as a possible route of delivery to the central nervous system for oxytocin . AKH has a similar structure to that of oxytocin, and its central effects seem to be comparable to oxytocin in this study and in previous studies . However, oxytocin has more distinct effects than AKH in schizophrenia models in recent studies .…”

“…Additionally, in the AAPA test, some nonspecific factors, such as anxiety, can affect the results. In our recent study, we showed antidepressant and anxiolytic effects of AKH both after acute and chronic administration [9,18] anxiolytic effects [29]. Thus, the anxiolytic effect of AKH and modulating effect with MK-801 on anxiety could have increased the memory performance of animals in the AAPA test.…”

“…Additionally, in the AAPA test, some nonspecific factors, such as anxiety, can affect the results. In our recent study, we showed antidepressant and anxiolytic effects of AKH both after acute and chronic administration . NMDA antagonists such as MK‐801 are also known to possess anxiolytic effects .…”